Enzalutamide Demonstrates Positive Overall Survival Results in Non-Metastatic Hormone-Sensitive Prostate Cancer

Strategic Insights -

Recent positive topline overall survival (OS) results from the phase 3 EMBARK trial (NCT02319837) have demonstrated that enzalutamide, as a monotherapy and combined with leuprolide, met the key secondary end point with a statistically significant and clinically meaningful improvement in OS vs placebo plus leuprolide in patients with non-metastatic hormone-sensitive prostate cancer (nmHSPC) with biochemical recurrence at high risk for metastasis. These results were announced in a press release from the developers, Pfizer and Astellas Pharma. The safety results were consistent with the demonstrated profile of enzalutamide, with no new safety signals reported in the analysis.

Key Takeaways:

  • Enzalutamide plus leuprolide met the key secondary end point with a statistically significant and clinically meaningful improvement in OS vs placebo plus leuprolide in patients with non-metastatic hormone-sensitive prostate cancer (nmHSPC) with biochemical recurrence at high risk for metastasis.
  • Enzalutamide monotherapy also demonstrated a favorable OS trend vs placebo plus leuprolide, although it was not statistically significant.
  • The safety results were consistent with the demonstrated profile of enzalutamide, with no new safety signals reported in the analysis.
  • The EMBARK trial randomly assigned, in a 1:1:1 ratio, a total of 1068 patients to receive enzalutamide plus leuprolide (n = 355), placebo plus leuprolide (n = 358), or enzalutamide monotherapy (n = 355).
  • The trial's primary end point was metastasis-free survival (MFS) in the enzalutamide plus leuprolide group vs placebo plus leuprolide.
  • Additional eligibility criteria for the trial included high-risk disease, a serum testosterone level of 150 ng per deciliter or higher, and an ECOG performance status of 0 or 1.

Statistics:

  • 87.3% (95% CI, 83.0%-90.6%) of patients in the enzalutamide plus leuprolide arm achieved 5-year MFS.
  • 71.4% (95% CI, 65.7%-76.3%) of patients in the placebo plus leuprolide group achieved 5-year MFS.
  • The risk of metastasis or death was 57.6% lower with the enzalutamide combination (HR, 0.42; 95% CI, 0.30-0.61; P < 0.001).
  • 80.0% (95% CI, 75.0%-84.1%) of patients in the enzalutamide monotherapy group achieved 5-year MFS.
  • The risk of metastasis or death was 36.9% lower with monotherapy vs placebo plus leuprolide (HR, 0.63; 95% CI, 0.46-0.87; P = 0.005).

Sources:

  • XTANDI® plus leuprolide significantly improves survival outcomes in men with non-metastatic hormone-sensitive prostate cancer with high-risk biochemical recurrence. News release. Pfizer and Astellas Pharma. July 10, 2025. Accessed July 10, 2025.
  • Pfizer and Astellas' Xtandi approved by U.S. FDA in earlier prostate cancer setting. News release. Astellas. November 17, 2023. Accessed July 10, 2025.
  • Astellas' XTANDI™ (Enzalutamide) granted European Commission approval for use in additional recurrent early prostate cancer treatment setting. News release. Astellas. April 23, 2024. Accessed July 10, 2025.
  • Freedland SJ, de Almeida Luz M, De Giorgi U, et al. Improved outcomes with enzalutamide in biochemically recurrent prostate cancer. N Engl J Med. 2023;389(16):1453-1465. doi:10.1056/NEJMoa2303974